Guselkumab

What is guselkumab?

Guselkumab is a biologic treatment indicated for moderate to severe psoriasis.

The U.S. Food and Drug Administration (FDA) has approved guselkumab (Janssen Biotech, PA, USA; TREMFYA™) for the treatment of adults living with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Guselkumab is the first and only approved biologic therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis.

Applications seeking approval of guselkumab in the European Union, Japan and other countries are currently under review.

Severe plaque psoriasis

What is guselkumab used for?

Guselkumab is used for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (ultraviolet light treatment).

It is not known if guselkumab is safe and effective in children under 18 years of age.

How does guselkumab work?

Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor.

While IL-23 promotes the normal inflammatory and immune responses, the p19 and p40 subunits of IL-23 are found to be over-expressed in the condition of psoriasis and other autoimmuneinflammatory skin diseases.

Guselkumab selectively binds to the p19 subunit of IL-23 in dendritic cells and keratinocytes and blocks its interaction with IL-23 receptor, which further prevents the release of other pro-inflammatorycytokines and chemokines via stimulation of immune cells such as Th17 cells.

Drug interactions with guselkumab

No data are available on the ability of live or inactive vaccines to elicit an immune response in patients receiving treatment with guselkumab.

Live vaccines should not be used concomitantly during guselkumab treatment.

Population pharmacokinetic analyses have indicated that concomitant use of ibuprofen, acetylsalicylic acid, or acetaminophen/paracetamol does not affect the clearance of guselkumab.

The effect of drugs metabolised via the hepatic cytochrome P450 enzymes such as warfarin and ciclosporin may be altered during concomitant administration with guselkumab.

Dosage modification of these drugs should be considered.

Results from an exploratory drug-drug interaction study in subjects with moderate-to-severe psoriasis have suggested a low potential for clinically relevant drug interactions for drugs metabolised by CYP3A4 (midazolam), CYP2C9 (warfarin), CYP2C19 (omeprazole) and CYP1A2 but the interaction potential cannot be ruled out for drugs metabolised by CYP2D6.

Contraindications to guzelkumab

Guzelkumab should not be used in patients that:

have an infection that does not go away or that keeps coming back

have tuberculosis (TB) or have been in close contact with someone with TB

recently received or are scheduled to receive a vaccine

plan to become pregnant

breastfeeding or plan to breastfeed.

Guselkumab is promising for plaque psoriasis in phase 3 studies.

Guselkumab has shown an acceptable safety profile and good efficacy in the treatment of moderate-to-severe plaque psoriasis.

It is a first-in-class biologic therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis.

Clinical trial findings have also demonstrated the effectiveness of guselkinuab in patients who had an inadequate response to treatment with ustekinumab.

A Phase 3 study evaluating guselkumab in the treatment of active psoriatic arthritis is ongoing, and a Phase 3 program evaluating the efficacy of guselkumab compared with secukinumab in the treatment of moderate to severe plaque psoriasis is underway.

Although further studies are needed to assess long-term safety and efficacy, based on the results to date, guselkumab appears to be a promising therapeutic option for moderate-to-severe plaque-type psoriasis.